Ergot alkaloid, 5-HT1B/1D and alpha-adrenoceptor agonist
Brand names: Migranal, D.H.E. 45, Trudhesa
Updated · Methodology
Third line
Dihydroergotamine is a third-line option for acute migraine when triptans failed or are contraindicated. SEN reserves it for backup use. Available as nasal spray (Migranal), subcutaneous or intramuscular injection. Onset 30 minutes to 2 hours. Maximum 3 mg/day and 6 mg/week.
Sources
ICD-10: G43.9 · ICD-11: 8A80.Z
Activates 5-HT1B/1D receptors on intracranial vessels, causing vasoconstriction that blocks pulsatile pain afferents in migraine. Alpha-adrenergic activity adds peripheral vasoconstriction. Metabolised by CYP3A4 – strong CYP3A4 inhibitors (macrolides, azoles, ritonavir, cobicistat) raise concentration manifold and risk fatal ergotism.
Contraindicated in pregnancy: triggers uterine contraction and reduces uteroplacental blood flow.
Passes into milk. Breastfeeding not recommended.
Reference information, not a clinical decision. Discuss feeding pauses or changes with your physician or an IBCLC.
7 pairs found. Sorted from critical to minor.
Mechanism
Both drugs constrict blood vessels. Almotriptan stimulates serotonin receptors in artery walls, including the coronary arteries, and dihydroergotamine acts on the same receptors and also on adrenergic receptors. Triptans can cause coronary artery spasm and ergot drugs cause prolonged vasospasm, so their vasoconstrictor effects may add up. In a study of 12 healthy volunteers, oral almotriptan with ergotamine (the closest relative of dihydroergotamine) caused no extra vasospasm, but an additive effect is theoretically possible.
Symptoms
Coronary spasm shows as pressure, pain or heaviness in the chest, throat, neck or jaw, and can progress to myocardial infarction or dangerous arrhythmias. Spasm of other arteries can cause cold, pale or numb fingers, abdominal pain with bloody diarrhoea from bowel ischaemia, sudden loss of vision or signs of stroke. Dihydroergotamine can also raise blood pressure sharply.
Management
The combination is contraindicated (almotriptan ficha técnica, Spanish Agency of Medicines, AEMPS: ergotamine and its derivatives; almotriptan and dihydroergotamine labels, US Food and Drug Administration, ). Keep at least 24 hours between the two drugs, in either order (almotriptan and dihydroergotamine labels, FDA). The shorter 6-hour interval after almotriptan in the Spanish ficha técnica refers to ergotamine. For dihydroergotamine, keep 24 hours both ways (FDA labels). If chest, throat, neck or jaw pain or tightness appears after a dose, withhold further doses and assess the patient for cardiac ischaemia (almotriptan ficha técnica, AEMPS). If cold, pale fingers, abdominal pain with blood in the stool or vision loss appear after a dose, assess arterial blood flow (almotriptan label, FDA). Taking triptans and ergot drugs, alone or together, on 10 or more days a month can lead to medication overuse headache (dihydroergotamine label, FDA).
Sources
Mechanism
Clarithromycin inhibits CYP3A4 – dihydroergotamine accumulates 5-10 fold. Fatal ergotism.
Symptoms
Limb ischaemia, myocardial infarction.
Management
Combination contraindicated.
Sources
Mechanism
Strongest CYP3A4 inhibitor – dihydroergotamine rises 20+ fold.
Symptoms
Fatal ergotism.
Management
Combination contraindicated.
Sources
Mechanism
Both drugs constrict blood vessels. Naratriptan stimulates serotonin receptors in the walls of cranial vessels. Dihydroergotamine acts on the same serotonin receptors and also on alpha-adrenergic receptors. Ergot drugs cause prolonged vasospasm and triptans can cause coronary artery spasm, so the vasoconstrictor effects of the two drugs may add up. Data on the combination are limited. In these data, naratriptan with ergotamine, dihydroergotamine or sumatriptan did not change blood pressure, heart rate or the electrocardiogram, and did not affect naratriptan blood levels. Still, the combination may in theory raise the risk of coronary artery spasm.
Symptoms
Tightness, pain or pressure in the chest, throat, neck and jaw is common after naratriptan. It is usually not cardiac but can be a sign of coronary artery spasm. Myocardial infarction, ventricular tachycardia and ventricular fibrillation have been reported within a few hours of triptan use, and also after dihydroergotamine. Spasm of other arteries causes numb, cold, pale or bluish fingers and toes, muscle pain, abdominal pain with bloody diarrhoea from bowel ischaemia, and sometimes splenic infarction. Both drugs can raise blood pressure sharply, and hypertensive crisis has been reported after triptans.
Management
The naratriptan summary of product characteristics (SmPC) from the Spanish Agency of Medicines and Medical Devices (AEMPS) contraindicates ergotamine and its derivatives (sections 4.3 and 4.5). The naratriptan and dihydroergotamine labels from the US Food and Drug Administration () also contraindicate the combination. Keep at least 24 hours between the two drugs, in either order (naratriptan and dihydroergotamine labels, FDA). The Spanish naratriptan SmPC sets the same 24-hour interval in both directions for ergotamine preparations (AEMPS). If chest pain or tightness spreading to the throat appears after a naratriptan dose and suggests cardiac ischaemia, give no further doses and evaluate the patient (naratriptan SmPC, AEMPS). If signs of vasospasm appear, such as cold, pale or bluish fingers, muscle pain or abdominal pain with blood in the stool, stop dihydroergotamine at once (dihydroergotamine label, FDA). Rule out vasospasm before the next naratriptan dose (naratriptan label, FDA). Monitor blood pressure (naratriptan label, FDA). Both drugs are contraindicated in uncontrolled hypertension (naratriptan and dihydroergotamine labels, FDA), and naratriptan also in moderate or severe hypertension (naratriptan SmPC, AEMPS). Taking triptans and ergot drugs, alone or together, on 10 or more days a month can lead to medication overuse headache (naratriptan and dihydroergotamine labels, FDA).
Sources
Mechanism
Ritonavir is the strongest ARV CYP3A4 inhibitor. Fatal ergotism.
Symptoms
Digital ischaemia, stroke.
Management
Combination contraindicated.
Sources
Mechanism
Both are 5-HT1B/1D vasoconstrictors. Additive coronary and peripheral vasospasm. – at least 24-hour washout.
Symptoms
Myocardial ischaemia, stroke within hours.
Management
Combination contraindicated. At least 24 hours between doses.
Mechanism
Voriconazole strongly inhibits the liver enzyme CYP3A4, and this enzyme breaks down dihydroergotamine. The combination has not been studied, but voriconazole is likely to raise dihydroergotamine blood levels and can cause ergotism (poisoning by ergot alkaloids). Higher dihydroergotamine levels raise the risk of vasospasm leading to ischaemia of the brain and limbs. Serious and life-threatening ischaemia has been reported when dihydroergotamine was combined with strong CYP3A4 inhibitors, including antifungals.
Symptoms
With excess dihydroergotamine, the arms and legs become numb, tingling and painful. The fingers and toes turn cold, pale or bluish, and pulses in the arms and legs weaken or disappear. Leg ischaemia causes cramping and pain in the legs or hips, heaviness or tightness in the leg muscles, burning or aching pain in the feet at rest, and a cold feeling or colour change in one or both legs. Brain ischaemia causes slurred speech and sudden weakness. Severe poisoning can bring nausea, vomiting, abdominal pain, respiratory depression, a rise and then usually a fall in blood pressure, confusion, delirium, seizures and coma. Persistent vasospasm in people with poor circulation can lead to gangrene or death.
Management
The voriconazole documents contraindicate the combination: the summary of product characteristics (SmPC) of the European Medicines Agency (, sections 4.3 and 4.5), the SmPC of the Spanish Agency of Medicines and Medical Devices (AEMPS, section 4.3) and the label of the US Food and Drug Administration (, sections 4 and 7). Dihydroergotamine is contraindicated with strong inhibitors of the enzyme CYP3A4 (dihydroergotamine labels, FDA). Voriconazole is a strong inhibitor of this enzyme (voriconazole SmPC, EMA, and label, FDA). If the two drugs have been taken together and signs of vasospasm appear, stop dihydroergotamine at once and get emergency medical help (dihydroergotamine labels, FDA). Such signs include numb, cold, pale or bluish fingers, cramping and pain in the legs, slurred speech or sudden weakness. For overdose, stop dihydroergotamine, give general supportive care with monitoring of vital signs, and observe the patient for at least 24 hours or while symptoms persist (dihydroergotamine label, FDA).
Sources
Verbatim lines from the interaction sections, in the language of the label
«CONTRAINDICATIONS: with recent use (i.e., within 24 hours) of other 5-HT 1 agonists or ergotamine-containing or ergot-type medications [see Drug Interactions (7.2) ]»FDA, section 4 · Open on DailyMed
«Triptans: Triptans (serotonin [5-HT] 1B/FDA, section 7 · Open on DailyMed
«CONTRAINDICATIONS: with concomitant use of strong CYP3A4 inhibitors [see Warnings and Precautions (5.1) and Drug Interactions (7.1) ]»FDA, section 4 · Open on DailyMed
«DRUG INTERACTIONS: Beta Blockers/FDA, section 7 · Open on DailyMed
«Selective Serotonin Reuptake Inhibitors: Weakness, hyperreflexia, and incoordination have been reported rarely when 5-HT 1 agonists have been co-administered with selective serotonin reuptake…»FDA, section 7 · Open on DailyMed
«Selective Serotonin Reuptake Inhibitors: Weakness, hyperreflexia, and incoordination have been reported rarely when 5-HT 1 agonists have been co-administered with selective serotonin reuptake…»FDA, section 7 · Open on DailyMed
«DRUG INTERACTIONS: Beta Blockers/FDA, section 7 · Open on DailyMed
«Selective Serotonin Reuptake Inhibitors: Weakness, hyperreflexia, and incoordination have been reported rarely when 5-HT 1 agonists have been co-administered with selective serotonin reuptake…»FDA, section 7 · Open on DailyMed
«Beta Blockers: There have been reports that propranolol may potentiate the vasoconstrictive action of ergotamine by blocking the vasodilating property of epinephrine.»FDA, section 7 · Open on DailyMed
«Selective Serotonin Reuptake Inhibitors: Weakness, hyperreflexia, and incoordination have been reported rarely when 5-HT 1 agonists have been co-administered with selective serotonin reuptake…»FDA, section 7 · Open on DailyMed
«Ergotamine-Containing and Ergot-Type Medications: Do not use almotriptan tablets and ergotamine-containing or ergot-derived medications like dihydroergotamine, ergotamine tartrate, or methysergide…»FDA, section 4 · Open on DailyMed
«CONTRAINDICATIONS: Ergot Derivatives Dihydroergotamine, ergonovine, ergotamine, methylergonovine»FDA, section 4 · Open on DailyMed
«La administración concomitante de claritromicina con alcaloides del cornezuelo del centeno (p. ej., ergotamina y dihidroergotamina) está contraindicada, por su efecto de ergotoxicidad (ver sección…»AEMPS, section 4.3 · Open on CIMA
«CONTRAINDICATIONS: Ergot alkaloids (ergotamine or dihydroergotamine) (4.6)»FDA, section 4 · Open on DailyMed
«CONTRAINDICATIONS: Ergot Derivatives: dihydroergotamine, ergotamine, methylergonovine»FDA, section 4 · Open on DailyMed
«derivados del cornezuelo de centeno (p.ej., dihidroergotamina, ergometrina, ergotamina, metilergonovina)»AEMPS, section 4.3 · Open on CIMA
«CONTRAINDICATIONS: • Alpha 1-adrenoreceptor antagonist: alfuzosin • Anti-gout: colchicine, in patients with renal and/FDA, section 4 · Open on DailyMed
«CONTRAINDICATIONS: Recent use (i.e., within 24 hours) of another 5-hydroxytryptamine 1 (5-HT 1 ) agonist, ergotamine-containing medication, or ergot-type medication such as dihydroergotamine (DHE) or…»FDA, section 4 · Open on DailyMed
«Tratamiento simultáneo con astemizol, terfenadina, disopiramida, cisaprida, pimocida, alcaloides del cornezuelo (como la ergotamina y la dihidroergotamina), simvastatina, atorvastatina o lovastatina.»AEMPS, section 4.3 · Open on CIMA
«CONTRAINDICATIONS: Recent use (i.e., within 24 hours) of another 5-HT 1 agonist, an ergotamine containing or ergot-type medication such as dihydroergotamine (DHE) or methysergide [see Drug…»FDA, section 4 · Open on DailyMed
«Analgésicos; Anestésicos: Alcaloides ergotamínicos (p.ej., dihidroergotamina, ergometrina, ergotamina, metilergometrina)»AEMPS, section 4.3 · Open on CIMA
«Drug Interactions: Additionally, the following other drugs are contraindicated with ketoconazole tablets: methadone, disopyramide, dronedarone, ergot alkaloids such as dihydroergotamine, ergometrine…»FDA, section 4 · Open on DailyMed
«Alcaloides ergóticos (ergotamina, dihidroergotamina, ergometrina), ya que el incremento de las concentraciones plasmáticas de estos fármacos puede provocar ergotismo.»AEMPS, section 4.3 · Open on CIMA
«La administración concomitante de naratriptán con ergotamina, preparados que contengan ergotamina, dihidroergotamina (DHE) o sumatrip tán no produjo efectos clínicamente significativos en la presión…»AEMPS, section 4.5 · Open on CIMA
«CONTRAINDICATIONS: Recent use (i.e., within 24 hours) of another 5-HT 1 agonist, ergotamine-containing medication, ergot-type medication (such as dihydroergotamine or methysergide) [see Drug…»FDA, section 4 · Open on DailyMed
«Alcaloides del ergot: Posaconazol puede aumentar la concentración plasmática de los alcaloides del ergot (ergotamina y dihidroergotamina), que pueden dar lugar a ergotismo. La administración…»AEMPS, section 4.5 · Open on CIMA
«Use with Ergot Alkaloids: Posaconazole may increase the plasma concentrations of ergot alkaloids (ergotamine and dihydroergotamine) which may lead to ergotism [see Drug Interactions (7.2) ] .»FDA, section 4 · Open on DailyMed
«Aumento o disminución de los niveles del medicamento concomitante: Dihidroergotamina, ergonovina, ergotamina, metilergonovina.»AEMPS, section 4.3 · Open on CIMA
«CONTRAINDICATIONS: Ergot Derivatives: dihydroergotamine, ergotamine, methylergonovine»FDA, section 4 · Open on DailyMed
«Ergot-Containing Drugs: Ergot-containing drugs have been reported to cause prolonged vasospastic reactions. Because these effects may be additive, use of ergotamine-containing or ergot-type…»FDA, section 7 · Open on DailyMed
«CONTRAINDICATIONS: Recent use (i.e., within 24 hours) of ergotamine-containing medication, ergot-type medication (such as dihydroergotamine or methysergide), or another 5-hydroxytryptamine 1 (5-HT 1…»FDA, section 4 · Open on DailyMed
«Alcaloides ergotamínicos (p. ej.: ergotamina y dihidroergotamina)»AEMPS, section 4.3 · Open on CIMA
«CONTRAINDICATIONS: Coadministration of voriconazole tablets with ergot alkaloids (ergotamine and dihydroergotamine) is contraindicated because voriconazole tablets may increase the plasma…»FDA, section 4 · Open on DailyMed
«CONTRAINDICATIONS: • Recent use (i.e., within 24 hours) of another 5-HT 1 agonist, ergotamine-containing medication, or ergot-type medication (such as dihydroergotamine or methysergide) [see Drug…»FDA, section 4 · Open on DailyMed
«Ergotamine: Oral administration of nitroglycerin markedly decreases the first-pass metabolism of dihydroergotamine and subsequently increases its oral bioavailability. Ergotamine is known to…»FDA, section 7 · Open on DailyMed
«Historia de hemorragia cerebral o con factores de riesgo que puedan aumentar el riesgo de hemorragia cerebral. Esto se debe a la actividad alfa-mimética de pseudoefedrina, en asociación con otros…»AEMPS, section 4.3 · Open on CIMA
«Sustratos CYP P450 3A4: Otros medicamentos metabolizados por el citocromo P450 3A4: ejemplos de dichos medicamentos son lidocaína, sirolimus, tacrolimus, sildenafilo, fentanilo, midazolam, triazolam…»AEMPS, section 4.5 · Open on CIMA
«En ensayos clínicos con cafeína/AEMPS, section 4.5 · Open on CIMA
«El mononitrato de isosorbida puede aumentar el efecto hipertensor de la dihidroergotamina (p.e.incrementando la presión arterial sistólica en bipedestación), debido al aumento de la biodisponibilidad…»AEMPS, section 4.5 · Open on CIMA
«Los informes sugieren que cuando se administra simultáneamente, la nitroglicerina, puede aumentar los niveles en sangre de la dihidroergotamina y sus efectos. Es necesaria una especial atención en…»AEMPS, section 4.5 · Open on CIMA
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Dihydroergotamine is evaluated for the following indications with varying evidence strength: Acute migraine attack (evidence tier B). See the full indication matrix with dosing and citations above on this page.
Common side effects of Dihydroergotamine (≥ 1 in 100): Nausea, vomiting, Nasal congestion, Paresthesia, Muscle cramps. See the Safety section for uncommon and serious reactions.
Contraindicated in pregnancy: triggers uterine contraction and reduces uteroplacental blood flow.
Passes into milk. Breastfeeding not recommended.
Dihydroergotamine is contraindicated in: Pregnancy, breastfeeding; Strong CYP3A4 inhibitors (clarithromycin, itraconazole, ritonavir, cobicistat); Triptans within 24 hours; Ischemic heart disease; Uncontrolled hypertension. Full list in the Safety section.
Direct links to regulator labels. Open in a new tab.
Eletriptan, Ergotamine, Fentanyl, Frovatriptan, Naratriptan, Palmitoylethanolamide, Tramadol, Meperidine